Characterization of vinblastine-induced supersensitivity in the rat

A single dose of vinblastine (3 mg/kg, i.v.) in the rat produced a long lasting depletion of endogenous (-)noradrenaline (NA) in atria as well as in vasa deferentia, the depletion being greater in atria than in vasa deferentia. The maximum depletion of NA in atria occurred between 60 and 90 h after vinblastine, while in vasa deferentia the maximum depletion was 35%, 120 h after vinblastine. The 30 min in vitro uptake of (-)-(3H) NA in atria was inhibited between 78 and 83% at 30, 60 and 120 h after vinblastine. In vasa deferentia the maximum inhibition of 25% was seen 15 h after vinblastine, however the NA uptake had returned to control level between 60 and 120 h after vinblastine. The effect of vinblastine pretreatment on the sensitivity of atria to NA and (-)isoprenaline(ISOP), and of vasa deferentia to NA, (-)phenylephrine (PHE), and methoxamine (ME) was evaluated. It was found that atria became highly sensitive to the (+) chronotropic effect of NA without significant change in sensitivity to ISOP. The sensitivity of vas deferens to NA and PHE was moderately increased without significantly affecting the sensitivity to ME. The magnitude of the supersensitivity was expressed in terms of the ratio of the geometric mean ED50 of an agonist in control tissue to that obtained in the same tissue from treated animals. The sensitivity of atria to NA increased 1.5, 3.9, 7.8, and 6.7 fold, 15, 30, 60 and 120 h after vinblastine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)